transketolase

Transketolase is a thiamine diphosphate (thiamine pyrophosphate, TPP)–dependent enzyme that catalyzes two-carbon transfer reactions in the non-oxidative phase of the pentose phosphate pathway (PPP). It helps rearrange carbon skeletons to connect the PPP with glycolysis, balancing production of ribose-5-phosphate for nucleotide synthesis with the generation of glycolytic intermediates.

Mechanism and reactions: Transketolase transfers a two-carbon unit from a ketose donor, xylulose-5-phosphate, to an aldose acceptor. In the first reaction, Xu5P donates two carbons to ribose-5-phosphate to yield glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate. In the second reaction, Xu5P again donates two carbons to erythrose-4-phosphate (or a related acceptor) to form glyceraldehyde-3-phosphate and fructose-6-phosphate. Both steps require a Mg2+ cofactor and the TPP prosthetic group within a dimeric enzyme.

Structure and localization: In most organisms, transketolase is a soluble cytosolic enzyme that forms a homodimer, with each subunit binding TPP at its active site. The enzyme is highly conserved from bacteria to humans, reflecting its central role in carbon metabolism.

Physiological role: By interconverting sugar phosphates, transketolase provides ribose-5-phosphate for nucleotide biosynthesis and channels carbon back into glycolysis when PPP flux is high. This supports cellular proliferation, anabolic growth, and responses to metabolic demands.

Clinical relevance: Red blood cell transketolase activity is used as an indicator of thiamine (vitamin B1) status because the holoenzyme requires TPP. Thiamine deficiency can impair transketolase activity and PPP function, contributing to broader energy metabolism disruption.